Interferon (IFN), the potent anti-viral compound which has been shown to posses anti-proliferative and immune regulatory activities, can enhance the expression of cell surface tumor associated and histocompatability antigens on human breast (MCF-7) and colon (WIDR) carcinoma cells. Treatment of MCF cells with increasing amounts of recombinant human leukocyte A IFN results in a dose-dependent increase in the binding of several monoclonal antibodies which recognize distinct cell surface antigens. For example, leukocyte A IFN/ml increased the binding of monoclonal B72.3 to a 220-400 K dalton cell surface antigen. The expression of a histocompatibility antigen, HLA-a,b,c, was also enhanced following IFN treatment. In contrast, monoclonal B139 which binds to a common determinant on all human normal and tumor cells is not effected by IFN treatment, suggesting a differential effect for IFN on tumor-associated and normal, constitutive antigens. The enhanced antigen expression is maximal within 16-24 hours after IFN addition. Clones of the MCF-7 cells express widely variable constitutive levels of tumor-associated antigens and their responsiveness to IFN is also widely varied suggesting clonal variation to the IFN-induced enhancement of these gene products. In MCF-7 clones not expressing a constitutive level of a tumor associated antigen, IFN treatment does not initiate the expression of that gene product. The IFN induced increase of monoclonal binding to the surface of human colon carcinoma cells WIDR, was similar to that described for MCF-7 cells. However, a clone line of the WIDR cell, C3-6, is unresponsive to the antigen enhancing activities of IFN but can be growth inhibited by IFN. These findings indicate that two distinct biological activities of IFN, anti-proliferation and enhanced expression of tumor-associated antigens, can be functionally separated within a single cell type. These studies also demonstrate that recombinantly derived human leukocyte A IFN can increase the presenttion of tumor-associated antigens to the surface of human breast and colon carcinoma cells which may be used as an adjuvant to the use of monoclonal antibodies for the detection and treatment of human cancer.